In CLL With Coexisting Conditions, Chlorambucil Produces Better Outcomes With Obinutuzumab Than With Rituximab

A randomized phase III trial conducted in 26 countries found that combining chlorambucil (Leukeran) with an anti-CD20 antibody—either obinutuzumab (Gazya) or rituximab (Rituxan)—produced better outcomes among patients with previously untreated chronic lymphocytic leukemia (CLL) and coexisting conditions than treating these patients with chlorambucil alone. “Obinutuzumab-chlorambucil provided an overall advantage over chlorambucil alone and induced deeper and longer remissions than did rituximab-chlorambucil,” the researchers concluded.

The study involved 781 patients with a median age of 73 years. Patients were required to have “a clinically meaningful burden of coexisting conditions, as reflected by a score higher than 6 on the Cumulative Illness Rating Scale (CIRS) (range, 0 to 56, with higher scores indicating worse health status) or a creatinine clearance of 30 to 69 mL per minute,” the investigators explained in the report published in TheNew England Journal of Medicine. The median CIRS score at baseline was 8, and the median creatinine clearance was 62.

“Most patients (82%) had more than three coexisting conditions, and nearly one-third (27%) had at least one coexisting condition that was not well controlled at baseline according to CIRS grading,” the researchers noted. The study was designed by the German CLL Study Group and the sponsor, F. Hoffmann–La Roche.

Key Findings

Median progression-free survival was 11.1 months for chlorambucil alone, 16.3 months with rituximab-chlorambucil, and 26.7 months with obinutuzumab-chlorambucil. “Treatment with obinutuzumab-chlorambucil, as compared with rituximab-chlorambucil, resulted in prolongation of progression-free survival [hazard ratio = 0.39; 95% CI = 0.31–0.49; P < .001] and higher rates of complete response [20.7% vs 7.0%] and molecular response,” reported Valentin Goede, MD, of the Center of Integrated Oncology Cologne-Bonn and University Hospital Cologne, Germany, and colleagues. “Infusion-related reactions and neutropenia were more common among patients treated with the combination including obinutuzumab than with rituximab, but the risk of infection was not increased,” the investigators stated.

“The rate of induction of negative status for minimal residual disease was more than 10 times as high with obinutuzumab-chlorambucil as it was with rituximab-chlorambucil. The capacity of a treatment to result in low levels of minimal residual disease in bone marrow or peripheral blood was recently associated with improved overall survival, irrespective of the clinically assessed response status,” they wrote.

“With longer follow-up,” the authors continued, “the higher rate of eradication of minimal residual disease that was observed with obinutuzumab as compared with rituximab may lead to an overall survival benefit in addition to the improvement in progression-free survival.”